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Catalytic enantioselective synthesis of boron-stereogenic BODIPYs

Nature Synthesis volume 2, pages 564–571 (2023)Cite this article

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Abstract

Boron dipyrromethenes (BODIPYs) are a class of tetracoordinate boron compounds that have attracted considerable interest in recent decades due to their excellent spectroscopic properties and structural versatility, leading to their widespread applications in chemical, biological, pharmaceutical and materials science. However, BODIPYs possessing boron-stereogenic centres in enantioenriched forms are rare and catalytic methodology to enantioselectively prepare a boron-stereogenic BODIPY remains elusive. Here we report a palladium-catalysed protocol for the enantioselective synthesis of boron-stereogenic BODIPYs via a desymmetric intramolecular C–H arylation reaction. This method gives access to a wide range of highly functionalized boron-stereogenic BODIPYs, including six- to nine-membered boron heterocycles, with good to excellent enantioselectivities. The discrimination of the two α C–H bonds of the BODIPY core is enabled by the co-action of steric hindrance and attractive interaction in the catalytic chiral pocket. Photophysical properties, derivatizations and applications in chiral recognition of the obtained chiroptical BODIPYs are investigated. This work enriches the chemical diversity of chiroptical BODIPY dyes.

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Fig. 1: Research status of boron-stereogenic BODIPYs and design of catalytic enantioselective approach.
Fig. 2: Development of palladium-catalysed enantioselective C–H arylation towards N2O-type boron-stereogenic BODIPYs.
Fig. 3: Photophysical properties and synthetic applications.

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Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information files. Raw data are also available from the corresponding author on reasonable request. Materials and methods, experimental procedures, characterization data, 1H, 13C, 19F, 11B NMR spectra and mass spectrometry data are available in the Supplementary Information. The X-ray crystallographic coordinates for structures reported in this study have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number CCDC 2175350 (2w). These data can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/data_request/cif.

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Acknowledgements

We are grateful for financial support from the National Natural Science Foundation of China (22122102, 22101120, 22271134), the Guangdong Provincial Key Laboratory of Catalysis (2020B121201002), the Shenzhen Science and Technology Innovation Committee (JCYJ20190809142809370) and the Stable Support Plan Program of Shenzhen Natural Science Fund (contract number 20200925152450004).

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  1. These authors contributed equally: Bing Zu, Yonghong Guo.

Authors and Affiliations

  1. Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, China

    Bing Zu, Yonghong Guo, Li-Qing Ren & Chuan He

  2. Department of Chemistry, Colorado State University, Fort Collins, CO, USA

    Yingzi Li

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Contributions

B.Z., Y.G. and C.H. conceived the project. B.Z., Y.G. and L.-Q.R. designed and performed the synthetic experiments. Y.L. designed and performed the computational studies. B.Z., Y.G., Y.L. and C.H. prepared the manuscript.

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Correspondence to Yingzi Li or Chuan He.

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Nature Synthesis thanks José Alemán, Hua Lu, Jolene Reid and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary handling editor: Peter Seavill, in collaboration with the Nature Synthesis team.

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Experimental details, supplementary sections 1–16, figs. 1–15 and tables 1–7.

Supplementary Data 1

Crystallographic data for compound 2w, CCDC 2175350.

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Zu, B., Guo, Y., Ren, LQ. et al. Catalytic enantioselective synthesis of boron-stereogenic BODIPYs. Nat. Synth 2, 564–571 (2023). https://doi.org/10.1038/s44160-023-00262-1

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